Oncotarget

Research Papers:

Snail1 is required for the maintenance of the pancreatic acinar phenotype

Jordina Loubat-Casanovas, Raúl Peña, Núria Gonzàlez, Lorena Alba-Castellón, Santi Rosell, Clara Francí, Pilar Navarro and Antonio García de Herreros _

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Oncotarget. 2016; 7:4468-4482. https://doi.org/10.18632/oncotarget.6785

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Abstract

Jordina Loubat-Casanovas1, Raúl Peña1, Núria Gonzàlez1,2, Lorena Alba-Castellón1, Santi Rosell1,3, Clara Francí1, Pilar Navarro1, Antonio García de Herreros1,4

1Programa de Recerca en Càncer, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain

2Servei d’Oncologia Mèdica, Hospital del Mar, 08003 Barcelona, Spain

3Escola Superior Infermeria del Mar, Universitat Pompeu Fabra, 08003 Barcelona, Spain

4Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain

Correspondence to:

Antonio García de Herreros, e-mail: agarcia@imim.es

Keywords: Snail1, pancreatic mesenchymal cells, fibroblast activation, pancreas physiology, acinar-ductal metaplasia

Received: July 13, 2015     Accepted: November 25, 2015     Published: December 29, 2015

ABSTRACT

The Snail1 transcriptional factor is required for correct embryonic development, yet its expression in adult animals is very limited and its functional roles are not evident. We have now conditionally inactivated Snail1 in adult mice and analyzed the phenotype of these animals. Snail1 ablation rapidly altered pancreas structure: one month after Snail1 depletion, acinar cells were markedly depleted, and pancreas accumulated adipose tissue. Snail1 expression was not detected in the epithelium but was in pancreatic mesenchymal cells (PMCs). Snail1 ablation in cultured PMCs downregulated the expression of several β-catenin/Tcf-4 target genes, modified the secretome of these cells and decreased their ability to maintain acinar markers in cultured pancreas cells. Finally, Snail1 deficiency modified the phenotype of pancreatic tumors generated in transgenic mice expressing c-myc under the control of the elastase promoter. Specifically, Snail1 depletion did not significantly alter the size of the tumors but accelerated acinar-ductal metaplasia. These results demonstrate that Snail1 is expressed in PMCs and plays a pivotal role in maintaining acinar cells within the pancreas in normal and pathological conditions.


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